System and method for electrically ablating tissue of a patient

ABSTRACT

System for electrically ablating tissue of a patient through a plurality of electrodes includes a memory, a processor and a treatment control module stored in the memory and executable by the processor. The treatment control module generates an estimated treatment region based on the number of electrical pulses to be applied.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a Continuation of U.S. Non-Provisional applicationSer. No. 15/612,006, filed Jun. 2, 2017, which is a Continuation of U.S.Non-Provisional application Ser. No. 13/273,001, now U.S. Pat. No.9,700,368, filed Oct. 13, 2011, which claims the benefit of U.S.Provisional Application No. 61/392,905, filed Oct. 13, 2010, all ofwhich is incorporated by reference herein.

This application is also related to PCT International Application NumberPCT/US10/29243, filed Mar. 30, 2010 and entitled “System and Method forEstimating a Treatment Region for a Medical Treatment Device and forInteractively Planning a Treatment of a Patient” (hereinafter the “IRETreatment Application”), which is incorporated herein by reference.

This application is also related to PCT International Application NumberPCT/US10/36734, filed May 28, 2010 and entitled “System and Method forSynchronizing Energy Delivery to the Cardiac Rhythm”, which is alsoincorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates to a control system for controlling amedical treatment device. More particularly, the present applicationrelates to a system and method for electrically ablating tissue of apatient.

BACKGROUND OF THE INVENTION

Devices for delivering therapeutic energy such as an ablation deviceusing irreversible electroporation (IRE) include a pulse generator andone or more electrodes coupled to the generator. The pulse generatordelivers the therapeutic energy to a targeted tissue through theelectrodes, thereby causing ablation of the tissue.

Once a target treatment area/region is located within a patient, theelectrodes of the device are placed in such a way as to create atreatment zone that surrounds the target treatment region.

Prior to treatment, a treatment planning system is used to generate anestimated treatment region that completely covers the target treatmentregion. The estimated region is used by a physician to plan where toplace the electrodes in the patient.

This can be effective when the target area is relatively small, e.g.,less than 2 cm in length. However, when the target area is much larger,e.g., larger than 3 cm in length, the physician is forced to use a largenumber of electrodes, e.g., 4 or more electrodes. This makes accuratelyplacing the electrodes much more difficult as moving one electrodeaffects the spacing from all other electrodes.

Alternatively, the large target area can be divided into two or moresmaller areas and the treatment procedure for one area can be repeatedto cover the other divided areas. However, this makes the entiretreatment procedure much longer. The longer procedure makes it riskierfor the patient since the patient would have to stay on an operatingtable much longer with an exposed body portion to be treated. The longerprocedure also makes the procedure more expensive.

Therefore, it would be desirable to provide a system and method forelectrically ablating tissue of a patient more safely and efficiently.

SUMMARY OF THE DISCLOSURE

According to one aspect of the invention, a system for electricallyablating tissue of a patient through a plurality of electrodes isprovided. The system includes a memory, a processor and a treatmentcontrol module stored in the memory and executable by the processor. Thetreatment control module generates an estimated treatment region bytaking into account the relationship between the ablation size and thenumber of pulses to be applied. This allows treatment of relativelylarge target ablation regions more efficiently and accurately.

According to another aspect of the invention, a method of electricallyablating tissue of a patient through a plurality of electrodes isprovided. The method includes receiving positions of a plurality ofelectrodes and generating an estimated treatment region based on thereceived electrode positions and the number of pulses to be applied.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates several components of a medical treatment system totreat a patient according to the present invention.

FIG. 2 is a schematic diagram of a treatment control computer of thepresent invention.

FIG. 3 is a screen shot of an “Information” screen of a treatmentcontrol module showing various input boxes.

FIG. 4 is a screen shot of a “Probe Selection” screen of the treatmentcontrol module showing a side view and top view of the four probe arrayand an example of the general shape of the treatment zone that can begenerated by a four probe array.

FIG. 5 is a screen shot of a “Probe Placement Process” screen of thetreatment control module.

FIG. 6 illustrates an example of a three probe array defining threeindividual treatment zones, which combine to form a combined treatmentregion.

FIG. 7 illustrates details of the generator shown in FIG. 1.

FIG. 8 is a graph illustrating the relationship of the number of pulsesdelivered and the size of the actual ablation region according to thepresent invention.

FIG. 9 illustrates ablation regions of varying sizes according to thenumber of pulses delivered according to the present invention.

DETAILED DESCRIPTION OF INVENTION

Throughout the present teachings, any and all of the one, two, or morefeatures and/or components disclosed or suggested herein, explicitly orimplicitly, may be practiced and/or implemented in any combinations oftwo, three, or more thereof, whenever and wherever appropriate asunderstood by one of ordinary skill in the art. The various featuresand/or components disclosed herein are all illustrative for theunderlying concepts, and thus are non-limiting to their actualdescriptions. Any means for achieving substantially the same functionsare considered as foreseeable alternatives and equivalents, and are thusfully described in writing and fully enabled. The various examples,illustrations, and embodiments described herein are by no means, in anydegree or extent, limiting the broadest scopes of the claimed inventionspresented herein or in any future applications claiming priority to theinstant application.

One embodiment of the present invention is illustrated in FIG. 1. One ormore probes/electrodes 22 deliver therapeutic energy and are powered bya voltage pulse generator 10 that generates high voltage pulses astherapeutic energy such as pulses capable of irreversiblyelectroporating the tissue cells. In the embodiment shown, the voltagepulse generator 10 includes six separate receptacles for receiving up tosix individual probes 22 which are adapted to be plugged into therespective receptacle. The receptacles are each labeled with a number inconsecutive order. In other embodiments, the voltage pulse generator canhave any number of receptacles for receiving more or less than sixprobes.

In the embodiment shown, each probe 22 includes either a monopolarelectrode or bipolar electrodes having two electrodes separated by aninsulating sleeve. In one embodiment, if the probe includes a monopolarelectrode, the amount of exposure of the active portion of the electrodecan be adjusted by retracting or advancing an insulating sleeve relativeto the electrode. See, for example, U.S. Pat. No. 7,344,533, which isincorporated by reference herein. The generator 10 is connected to atreatment control computer 40 having input devices such as keyboard 12and a pointing device 14, and an output device such as a display device11 for viewing an image of a target treatment region such as a lesion300 surrounded by a safety margin 301. The pulse generator 10 is used totreat a lesion 300 inside a patient 15. An imaging device 30 includes amonitor 31 for viewing the lesion 300 inside the patient 15 in realtime. Examples of imaging devices 30 include ultrasonic, CT, MRI andfluoroscopic devices as are known in the art.

The present invention includes computer software (treatment controlmodule 54) which assists a user to plan for, execute, and review theresults of a medical treatment procedure, as will be discussed in moredetail below. For example, the treatment control module 54 assists auser to plan for a medical treatment procedure by enabling a user tomore accurately position each of the probes 22 of the pulse generator 10in relation to the lesion 300 in a way that will generate the mosteffective treatment zone. The treatment control module 54 can displaythe anticipated treatment zone based on the position of the probes andthe treatment parameters. The treatment control module 54 can displaythe progress of the treatment in real time and can display the resultsof the treatment procedure after it is completed. This information canbe used to determine whether the treatment was successful and whether itis necessary to re-treat the patient.

For purposes of this application, the terms “code”, “software”,“program”, “application”, “software code”, “software module”, “module”and “software program” are used interchangeably to mean softwareinstructions that are executable by a processor.

The “user” can be a physician or other medical professional. Thetreatment control module 54 executed by a processor outputs various dataincluding text and graphical data to the monitor 11 associated with thegenerator 10.

Referring now to FIG. 2, the treatment control computer 40 of thepresent invention manages planning of treatment for a patient. Thecomputer 40 is connected to the communication link 52 through an I/Ointerface 42 such as a USB (universal serial bus) interface, whichreceives information from and sends information over the communicationlink 52 to the voltage generator 10. The computer 40 includes memorystorage 44 such as RAM, processor (CPU) 46, program storage 48 such asROM or EEPROM, and data storage 50 such as a hard disk, all commonlyconnected to each other through a bus 53. The program storage 48 stores,among others, a treatment control module 54 which includes a userinterface module that interacts with the user in planning for, executingand reviewing the result of a treatment. Any of the software programmodules in the program storage 48 and data from the data storage 50 canbe transferred to the memory 44 as needed and is executed by the CPU 46.

In one embodiment, the computer 40 is built into the voltage generator10. In another embodiment, the computer 40 is a separate unit which isconnected to the voltage generator through the communication link 52. Ina preferred embodiment, the communication link 52 is a USB link.

In one embodiment, the imaging device 30 is a stand alone device whichis not connected to the computer 40. In the embodiment as shown in FIG.1, the computer 40 is connected to the imaging device 30 through acommunication link 53. As shown, the communication link 53 is a USBlink. In this embodiment, the computer can determine the size andorientation of the lesion 300 by analyzing the data such as the imagedata received from the imaging device 30, and the computer 40 candisplay this information on the monitor 11. In this embodiment, thelesion image generated by the imaging device 30 can be directlydisplayed on the grid 200 of the monitor 11 of the computer running thetreatment control module 54. This embodiment would provide an accuraterepresentation of the lesion image on the grid 200, and may eliminatethe step of manually inputting the dimensions of the lesion in order tocreate the lesion image on the grid 200. This embodiment would also beuseful to provide an accurate representation of the lesion image if thelesion has an irregular shape.

The basic functionality of the computer software (treatment controlmodule 54) will now be discussed in relation to the following example.

It should be noted that the software can be used independently of thegenerator 10. For example, the user can plan the treatment in adifferent computer as will be explained below and then save thetreatment parameters to an external memory device, such as a USB flashdrive (not shown). The data from the memory device relating to thetreatment parameters can then be downloaded into the computer 40 to beused with the generator 10 for treatment.

After the treatment control module 54 is initialized, it displays an“Information” screen with various input boxes as shown in FIG. 3. Akeyboard or other input device 12, together with a mouse or otherpointing device 14 (see FIG. 1) are used to input the data. Any datathat is inputted into the input boxes can be saved into internal orexternal memory along with a record of the treatment as described belowfor future reference. The basic patient information can be inputted,such as a patient ID number in input box 100, the name of the patient ininput box 101, and the age of the patient in input box 102. The user canenter clinical data, such as the clinical indication of the treatment ininput box 114. The date of the procedure is automatically displayed at111 or can be inputted by the user in another embodiment. The user canenter other case information such as the name of the physician in inputbox 112 and any specific case notes in input box 113.

The dimensions of the lesion 300 are determined from viewing it on themonitor 31 of the imaging device 30 (see FIG. 1) such as an ultrasonicimaging device and using known methods to calculate the dimensions fromthe image generated from the imaging device 31. The dimensions of thelesion 300 (length at input box 103, width at input box 104, and depthat input box 105) are inputted into the program. A safety margin isselected at input box 106 which will surround the entire lesion 300 inthree dimensions. According to the size of the safety margin that isselected, a target treatment region is automatically calculated and isdisplayed in boxes 107, 108, and 109 as shown. In one embodiment, thesafety margin value may be set to zero. For example, when treating abenign tumor, a safety margin may not be necessary.

In the embodiment shown in FIG. 3, the user has indicated that thelesion that will be treated has a length of 2 cm, width of 1 cm and adepth of 1 cm. With a user specified margin of 1 cm (which is a defaultmargin setting), the target treatment region has a length of 4 cm, widthof 3 cm and a depth of 3 cm.

The user can select the “ECG synchronization” option by clicking thecircle in the box 110 in order to synchronize the pulses with anelectrocardiogram (ECG) device, if such a device is being used duringthe procedure. The other options available for treatment that areincluded in box 110 can include an option for “90 PPM” (pulses perminute) or “240 PPM”. The user should select at least one of the threeoptions provided in box 110. After all of the necessary data has beeninputted, the user clicks on the “Next” button with a pointing device 14to proceed to the next screen described below.

Further regarding the ECG synchronization option, if this circle isselected in window 110, the treatment control module 54 will test thisfunctionality to verify that the system is working properly. Thetreatment control module 54 can automatically detect whether an errorhas occurred during the testing phase of the ECG feature. The detectableerrors include, but are not limited to, “no signal” (such as no pulsesfor 3.5 seconds) and “noisy” (such as pulses occurring at a rate greaterthan 120 beats per minute for at least 3.5 seconds).

The treatment control module 54 can synchronize energy release withcardiac rhythm by analyzing cardiac output such as electrocardiogramresults (or other cardiac function output) and sending synchronizationsignals to a controller of the pulse generator 10. The control module 54is also capable of generating internal flags such as a synchronizationproblem flag and a synchronization condition flag to indicate to userson a graphic user interface a synchronization status, so that energypulse delivery can be synchronized with the cardiac rhythm for each beat(in real-time) or aborted as necessary for patient safety and treatmentefficiency.

Specifically, the control module 54 synchronizes energy pulses such asIRE (irreversible electroporation) pulses with a specific portion of thecardiac rhythm. The module uses the R-wave of the heartbeat andgenerates a control signal to the pulse generator 10 indicating thatthis portion of the heartbeat is optimal for release of IRE pulses. Forclarity, the S wave would be an optimal time for delivery of an energypulse, but due to the fact that the S wave ends nebulously in somecases, the R wave is used as an indicator to start timing of energyrelease.

More specifically, the synchronization feature of the control module 54allows for monitoring of heart signals so as to ensure that changes,maladies, and other alterations associated with the heartbeat arecoordinated such that pulses from the pulse generator 10 are released atthe proper time, and that if the heartbeat is out of its normal rhythm,that the release of energy is either altered or aborted.

Next, the user can select the number of probes that the user believeswill be necessary to produce a treatment zone which will adequatelycover the lesion 300 and any safety margin 301. The selection is made byclicking the circle next to each type of device, as shown in the “ProbeSelection” screen, illustrated in FIG. 4.

In one embodiment, a “Probes Selection Status” box 199 identifies whichof the receptacles, if any, on the generator 10 have been connected to aprobe by displaying the phrase “Connected” or the like next to thecorresponding probe number. In one embodiment, each receptacle includesan RFID device and a connector for each probe which connects to thereceptacle and includes a compatible RFID device, so that the treatmentcontrol module 54 can detect whether or not an authorized probe has beenconnected to the receptacle on the generator 10 by detecting aconnection of the compatible RFID devices. If an authorized probe is notconnected to a receptacle on the generator, the phrase “Not Connected”or the like will appear next to the probe number. In addition, the colorof each probe shown in the “Probes Selection Status” box 199 can be usedto indicate whether or not each receptacle on the generator is connectedto a compatible probe. This feature allows the user to verify that therequisite number of probes are properly connected to the generator 10before selecting a probe type for the treatment procedure. For example,if the treatment control module 54 detects a problem with the probeconnection status (e.g. selecting a three probe array when only twoprobes are connected to the generator), it can notify the user bydisplaying an error message.

The user can select which of the connected probes will be used toperform the treatment procedure, by clicking on the box next to theselected probes in the “Probes Selection Status” box 199. By default thetreatment control module 54 will automatically select probes inascending numerical order, as they are labeled.

Referring to FIG. 4, circle 150 is used to select a four probe array.FIG. 4 illustrates a side view 151 and top view 152 of the four probearray and an example of the general shape of the treatment zone that canbe generated by a four probe array. In the illustrated example, theexposed portion of each of the electrodes as shown is 20 mm in lengthand each pair of the four probes are equally spaced from each other by15 mm, as measured at four places (PLCS) along the perimeter.

FIG. 5 illustrates a “Probe Placement Process” screen of one aspect ofthe invention. The screen illustrated by FIG. 5 shows a lesion 300according to the dimensions which were inputted on the “Information”screen (see FIG. 3) along with a safety margin 301, if any, that waspreviously inputted. In the example depicted in FIG. 5, the lesion 300has a length of 2.0 cm and a width of 1.0 cm, and the device selected onthe “Probe Selection” screen (see FIG. 4) is a four probe array. Thelesion 300 is displayed near the center of an x-y grid 200 with thedistance between two adjacent grid lines representing 1 mm. Each of thefour probes 201, 202, 203, 204 is displayed in the grid 200 and eachprobe can be manually positioned within the grid by clicking anddragging the probe with the pointing device 14. Two fiducials 208, 209labeled “A” and “B”, respectively, are also displayed on the grid 200and are used as a point of reference or a measure as will be describedbelow.

The amount of longitudinal exposure of the active electrode portion foreach probe that has already been manually adjusted by the user asexplained above can be manually inputted in input box 210, which can beselected by the user according to the depth (z) of the lesion. In thisway, the treatment control module 54 can generate an estimated treatmentzone according to the treatment parameters, and locations and depths ofthe probes. In one embodiment, a second x-z grid is displayed on themonitor 11 of the computer running the treatment control module 54. Inone embodiment, the treatment control module 54 can automaticallycalculate preferred values for the amount of longitudinal exposure ofthe active electrode portions based on the size and shape of the lesion.The depth (z) of the electric field image can be calculated analyticallyor with interpolation and displayed on the x-z grid. Because thedistribution of the electric field (i.e., expected treatment region)between two monopolar electrodes may “dip in” along the boundary line(e.g., a peanut shaped treatment region due to large spacing between thetwo electrodes where the width of the region is smaller in the middle;see for example region 305 in FIG. 9) depending on the electrodelocation and the applied voltage, it is beneficial to have an x-z gridincluded on the monitor. For example, if this “dip” of the boundary linetravels into, rather than surround/cover, the lesion region, then thetargeted region may not be fully treated. As a default to ensuretreatment of the entire lesion region, the probe depth placement and theexposure length may be set unnecessarily higher to ensure erring on thesafe side. However, this will potentially treat a much larger volumethan needed, killing healthy surrounding tissue, which can be an issuewhen treating sensitive tissues such as the pancreas, brain, etc. Byoptimizing the treatment depth (z) together with the width (x) andheight (y), this effect may be reduced, further enhancing proceduralprotocol and clinical outcome.

The probe dock status is indicated in box 210, by indicating if theprobes are “docked” or “undocked”. The “UnDock Probes” button allows theuser to “unplug” the probes from the generator while the “ProbePlacement Process” screen is displayed without causing error messages.In normal operation, the user plugs the probes into the generator on the“Probe Selection” screen, and then the probes are “authorized” as beingcompatible probes according to the RFID devices, as discussed above.When the user proceeds to the “Probe Placement Process” screen, thesoftware requires that all the selected probes remain plugged into thegenerator, or else the software will display an error message (e.g.“Probe #2 unplugged”, etc.), and will also force the user back to the“Probe Selection” screen. However, sometimes doctors may want to performanother scan of the lesion or perform some other procedure while leavingthe probes inserted in the patient. But, if the procedure cannot beperformed near the generator, the probes are unplugged from thegenerator. If the user selects the “UnDock Probes” button, this willallow the probes to be unplugged from the generator without causing anerror message. Then, after the user has performed the other procedurethat was required, he can re-attach the probes to the generator, andthen select “Dock Probes” in input box 210. In this way, the user willnot receive any error messages while the “Probe Placement Process”screen is displayed.

There is a default electric field density setting (Volts/cm) which isshown in input box 211. In the example, the default setting is 1500Volts/cm. This number represents the electric field density that theuser believes is needed to effectively treat the cells, e.g., ablate thetissue cells. For example, 1500 Volts/cm is an electric field densitythat is needed to irreversibly electroporate the tissue cells. Based onthe number selected in input box 211, the treatment control module 54automatically adjusts the voltage (treatment energy level) appliedbetween the electrodes, as shown in column 222.

Box 280 allows a user to select between two different Volts/cm types,namely “Linear” or “Non-Linear Lookup”.

The default Volts/cm setting is “Linear”, in which case the Voltage thatis applied between a given pair of electrodes, as shown in column 222,is determined by the following formula:Voltage=xd,  (1)

-   -   where x=the electric field density setting (Volts/cm) shown in        column 225, which is based on the value from box 211, and    -   where d=the distance (cm) between the given pair of electrodes        shown in column 226.        Therefore, when “Linear” is selected, the Voltage that is        applied between a given pair of electrodes is directly        proportional to the Distance between the given electrode pair in        a linear relationship.

If the user selects “Non-Linear Lookup” in box 280, then the Voltagethat is applied between the given pair of electrodes will be similar tothe Voltage values for a “Linear” selection when a pair of electrodesare closely spaced together (e.g. within about 1 cm). However, as a pairof given electrodes are spaced farther from one another, a “Non-LinearLookup” will produce lower Voltages between the given pair of electrodesas compared to the Voltage values for a “Linear” selection at any givendistance. The “Non-Linear Lookup” feature is particularly useful forreducing “popping” during treatment. “Popping” refers to an audiblepopping noise that sometimes occurs, which is believed to be caused by aplasma discharge from high voltage gradients at the tip of theelectrodes. The “Non-Linear Lookup” feature can also minimize anyswelling of the tissue that might occur as a result of a treatment. TheVoltage values used for the “Non-Linear Lookup” selection can bepre-determined based on animal experiments and other research. In oneembodiment, different tissue types can each have their own “Non-LinearLookup” table. In the example shown, the tissue being treated isprostate tissue.

The details of the treatment parameters are displayed in window 270. Thefiring (switching) sequence between probes is listed automatically inwindow 270. In the example, the firing sequence involves six stepsbeginning with between probes 1 and 2, then probes 1 and 3, then probes2 and 3, then probes 2 and 4, then probes 3 and 4, and then probes 4 and1. As shown, the polarity of each of the probes may switch from negativeto positive according to step of the firing sequence. Column 220displays which probe is the positive probe (according to a numberassigned to each probe) for each step. Column 221 displays which probeis the negative probe (according to a number assigned to each probe) foreach step. Column 222 displays the actual voltage generated between eachprobe during each step of the firing sequence. In the example, themaximum voltage that can be generated between probes is limited by thecapabilities of the generator 10, which in the example is limited to amaximum of 3000 Volts. Column 223 displays the length of each pulse thatis generated between probes during each respective step of the firingsequence. In the example, the pulse length is predetermined and is thesame for each respective step, and is set at 100 microseconds. Column224 displays the number of pulses that is generated during eachrespective step of the firing sequence. In the example, the number ofpulses is predetermined and is the same for each respective step, and isset at 90 pulses which are applied in a set of 10 pulses at a time.Column 225 displays the setting for Volts/cm according to the valueselected at input box 211. Column 226 displays the actual distancebetween the electrodes (measured in cm), which is automaticallycalculated according to the placement of each probe in the grid 200.

The treatment control module 54 can be programmed to calculate anddisplay the area of the combined treatment regions on the grid 200 byseveral different methods.

Each method determines a boundary line surrounding a treatment zone thatis created between a pair of electrodes. By combining a plurality oftreatment zones with each treatment zone being defined by a pair ofelectrodes, a combined treatment region can be displayed on the x-ygrid. FIG. 6 illustrates three electrodes 201 (E1), 202 (E2), 203 (E3)defining three individual treatment zones 311, 312, 313, which combineto form a combined treatment region 315 which is shown with hatchedlines.

As discussed above, the monitor can further include an x-z grid toillustrate the depth of the lesion and the shape of the treatmentregion. The shape of the treatment zone in the x-z grid will varyaccording to the selected amounts of electrode exposure for each probeand can be determined by one or more methods.

In one embodiment, the treatment boundary line that is created betweentwo points on the x-y grid can be rotated about an axis joining the twopoints in order to generate the treatment region boundary line on thex-z grid. In this embodiment, several points may be selected along theexposed length of the active electrode portion for each probe at variousdepths (z). A three-dimensional combined treatment region can then begenerated by determining the boundary line on the x-y grid between eachindividual pair of points and then rotating the boundary line along theaxis joining each pair of points. The resulting boundary lines can becombined to create a three dimensional image that is displayed on themonitor.

The following is an alternate method for determining a boundary line onthe x-z grid, thereby determining a three dimensional treatment region.This example describes a two probe array with the probes being insertedin a parallel relationship and with the probes having the same amount ofexposed portions of the electrode. In this example, the exposed portionsof each probe start at the same “uppermost” depth (z) and end at thesame “lowermost” depth (z). First, a treatment zone boundary line iscreated in the x-y plane at the uppermost depth (z). Next, the treatmentzone boundary line is repeatedly created stepwise for all subsequentlylower depths (z), preferably evenly spaced, until the lowermost depth(z) is reached. The result is a 3-D volume (stacked set of treatmentzone boundary lines) having a flat top surface and a flat bottomsurface. Next, two new focus points are selected, with the first focuspoint positioned midway between the probe positions in the x-y grid andnear the uppermost depth (z) of the exposed electrode. The second focuspoint is also positioned midway between the probe positions in the x-ygrid, but near the lowermost depth (z) of the exposed electrode. Next, atreatment zone boundary line is created in the x-z grid using one of themethods described earlier. The actual placement of each focus point maybe closer together, namely, not positioned in the uppermost andlowermost x-y planes defined by the exposed portions. The placement ofeach focus point should be selected so that the treatment zone boundaryline that is created in the x-z grid closely matches the treatment zoneboundary lines that were created in the uppermost and lowermost x-ygrids. Next, the treatment zone boundary line that was created in thex-z grid according to the two focus points is rotated about the axisjoining the two focus points. This creates the shapes for the upper andlower 3-D volumes which are added to the flat top surface and the flatbottom surface described above.

The above methods can be applied by persons of ordinary skill in the artto create 3-D treatment zones between exposed portions of electrodeseven when the probes are not parallel to each other and even when theamount of the exposed portion varies with each probe.

Furthermore, there are situations where it is advantageous to showmultiple boundary zones as a result of a therapy. For example,indicating which regimes undergo no change, reversible electroporation,irreversible electroporation, and conventional thermal damage ispossible in accordance with the present invention. In addition, it ispossible to output the entire distribution rather than just delineatingboundaries.

It has been shown repeatedly in the literature that tissue propertiesare highly variable between tissue types, between individuals, and evenwithin an individual. These changes may result from differences in bodyfat composition, hydration levels, and hormone cycles. Due to the largedependence of IRE (irreversible electroporation) treatments on tissueconductivity, it is imperative to have accurate values. Therefore, toobtain viable conductivity values prior to treatment, a low amplitudevoltage pulse is used between the electrode conductors and the resultantimpedance/conductance is measured as a way to determine pertinent tissueproperty data such as the predicted current. The value determined maythen be implemented when assessing field strength and treatment protocolin real time. For example, the resulting impedance or predicted currentcan be used to set the default electric field density.

One method of generating an estimated treatment region between a pair oftreatment electrodes is a numerical model based method involving finiteelement analysis (FEA). For example, U.S. Patent Application PublicationNo. 2007/0043345, which is hereby incorporated by reference, disclosesusing FEA models to generate treatment zones between a pair ofelectrodes (the calculations were performed using MATLAB's finiteelement solver, Femlab v2.2 (The MathWorks, Inc. Natick, Mass.)).

Most engineering problems can be solved by breaking the system intocells where each corner of the cell or mesh is a node. FEA is used torelate each node to each of the other nodes by applying sets of partialdifferential equations. This type of a system can be coded by scratch,but most people use one of many commercial FEA programs thatautomatically define the mesh and create the equations given the modelgeometry and boundary conditions. Some FEA programs only work in onearea of engineering, for example, heat transfer and others are known asmulitphysics. These systems can convert electricity to heat and can beused for studying the relationships between different types of energy.

Typically the FEA mesh is not homogeneous and areas of transition haveincreased mesh density. The time and resources (memory) required tosolve the FEA problem are proportional to the number of nodes, so it isgenerally unwise to have a uniformly small mesh over the entire model.If possible, FEA users also try to limit the analysis to 2D problemsand/or use planes of symmetry to limit the size of the model beingconsidered because even a modest 2D model often requires 30 minutes toseveral hours to run. By comparison, a 3D Model usually takes severalhours to several days to run. A complicated model like a weather systemor a crash simulation may take a super computer several days tocomplete.

Depending on the complexity of the FEA models that are required, thepurchase price of the FEA modeling software can cost several thousanddollars for a low end system to $30 k for a non linear multiphysicssystem. The systems that model the weather are custom made and cost tensof millions of dollars.

In one example, the steps which are required for generating a treatmentzone between a pair of treatment probes using finite element analysisinclude: (1) creating the geometry of interest (e.g., a plane of tissuewith two circular electrodes); (2) defining the materials involved(e.g., tissue, metal); (3) defining the boundary conditions (e.g.,Initial voltage, Initial temperature); (4) defining the system load(e.g., change the voltage of the electrodes to 3,000V); (5) determiningthe type of solver that will be used; (6) determining whether to use atime response or steady state solution; (7) running the model and waitfor the analysis to finish; and (8) displaying the results.

Using FEA, however, may not be practical for use in calculating anddisplaying in real time a treatment zone that is created between a pairof treatment probes in accordance with the present invention because ofthe time required to run these types of analyses. For the presentinvention, the system should allow a user to experiment with probeplacement and should calculate a new treatment zone in less than a fewseconds. Accordingly, the FEA model is not appropriate for such use andit would be desirable to find an analytic solution (closed formsolution), which can calculate the treatment zones with only simpleequations, but which closely approximate the solutions from a numericalmodel analysis such as the finite element analysis. The closed loopsolutions should preferably generate the treatment zone calculation in afraction of a second so as to allow a physician/user to experiment withprobe placement in real time.

There are different closed loop (analytical model analysis) methods forestimating and displaying a treatment zone between a pair of treatmentprobes, which produce similar results to what would have been derived bya numerical model analysis such as FEA, but without the expense and timeof performing FEA. Analytical models are mathematical models that have aclosed form solution, i.e., the solution to the equations used todescribe changes in a system can be expressed as a mathematical analyticfunction. The following method represents just one of the non-limitingexamples of such alternative closed loop solutions.

In mathematics, a Cassini oval is a set (or locus) of points in theplane such that each point p on the oval bears a special relation to twoother fixed points q₁ and q₂: the product of the distance from p to q₁and the distance from p to q₂ is constant. That is, if the functiondist(x,y) is defined to be the distance from a point x to a point y,then all points p on a Cassini oval satisfy the equation:dist(q ₁ ,p)×dist(q ₂ ,p)=b ²  (2)

-   -   where b is a constant.

The points q₁ and q₂ are called the foci of the oval.

Suppose q₁ is the point (a,0), and q₂ is the point (−a,0). Then thepoints on the curve satisfy the equation:(x−a)² +y ²)((x+ ^(a))² +y ²)=b ⁴  (3)

The equivalent polar equation is:r ⁴−2a ² r ² cos 2θ=b ⁴ −a ⁴  (4)

The shape of the oval depends on the ratio b/a. When b/a is greater than1, the locus is a single, connected loop. When b/a is less than 1, thelocus comprises two disconnected loops. When b/a is equal to 1, thelocus is a lemniscate of Bernoulli.

The Cassini equation provides a very efficient algorithm for plottingthe boundary line of the treatment zone that was created between twoprobes on the grid 200. By taking pairs of probes for each firingsequence, the first probe is set as q₁ being the point (a,0) and thesecond probe is set as q₂ being the point (−a,0).

The polar equation for the Cassini curve is preferably used because itprovides a more efficient equation for computation. The currentalgorithm can work equally as well by using the Cartesian equation ofthe Cassini curve. By solving for r² from eq. (4) above, the followingpolar equation was developed:r ² =a ² cos(2*theta)+/−sqrt(b ⁴ −a ⁴ sin²(2*theta))  (5)

-   -   where a=the distance from the origin (0,0) to each probe in cm;        and    -   where b is calculated from the following equation:

$\begin{matrix}{b^{2} = \lbrack \frac{V}{\lbrack {{{\ln(a)}(595.28)} + 2339} \rbrack( \frac{A}{650} )} \rbrack^{2}} & (6)\end{matrix}$

-   -   where V=the Voltage (V) applied between the probes;    -   where a=the same a from eq. (5); and    -   where A=the electric field density (V/cm) that is required to        ablate the desired type of tissue according to known scientific        values.

As can be seen from the mathematics involved in the equation, r can beup to four separate values for each given value for theta.

Example 1

If V=2495 Volts; a=0.7 cm; and A=650 V/cm;

Then b²=1.376377

and then a cassini curve can be plotted by using eq. (5) above bysolving for r, for each degree of theta from 0 degrees to 360 degrees.

A portion of the solutions for eq. (5) are shown in Table 1 below:

where M=a² cos(2*theta); and L=sqrt(b⁴−a⁴ sin²(2*theta))

TABLE 1 Theta r = sqrt r = −sqrt r = sqrt r = −sqrt (degrees) (M + L)(M + L) (M − L) (M − L) 0 1.366154 −1.36615 0 0 1 1.366006 −1.36601 0 02 1.365562 −1.36556 0 0 3 1.364822 −1.36482 0 0 4 1.363788 −1.36379 0 05 1.362461 −1.36246 0 0 6 1.360843 −1.36084 0 0 7 1.358936 −1.35894 0 08 1.356743 −1.35674 0 0 9 1.354267 −1.35427 0 0 10 1.351512 −1.35151 0 011 1.348481 −1.34848 0 0 12 1.34518 −1.34518 0 0 13 1.341611 −1.34161 00 14 1.337782 −1.33778 0 0 15 1.333697 −1.3337 0 0

The above eq. (6) was developed according to the following analysis.

The curve from the cassini oval equation was calibrated as best aspossible to the 650 V/cm contour line using two 1-mm diameter electrodeswith an electrode spacing between 0.5-5 cm and an arbitrary appliedvoltage.

For this worksheet, q₁ and q₂ reference points (taken to be+/−electrodes) could be moved to locations along the x-axis to points of(±a,0). A voltage could then be selected, and an arbitrary scalingfactor (“gain denominator”) would convert this voltage to thecorresponding “b” used in eq. (4). The worksheet would then plot theresulting Cassini oval, which has a shape progression with appliedvoltage beginning as two circles around the electrodes that grow intoirregular ellipses before converging into a single “peanut” shape thatultimately becomes an ellipse expanding from the original electrodelocations.

The Cassini oval creates a reasonable visualization that mimics theshape of numerical results for the field distribution. In order tounderstand which values or levels correspond to a desired electric fieldof interest, a calibration involving the b⁴ term was necessary todevelop the relationship between the analytical Cassini oval and thenumerical results. This was done through a backwards calibration processdefined as follows:

1. A reference contour was selected to correlate the analytical andnumerical solutions. This was chosen to be when b/a=1, forming alemniscate of Bernoulli (the point where the two ellipses first connect,forming “∞”).

2. A reference electric field density value was selected to be 650 V/cm.

3. Numerical models were developed to mimic the x-y output from theCassini oval for scenarios where a=±0.25, 0.5, 0.75, 1.0, 1.25, 1.5,1.75, 2.0, 2.25, and 2.5 cm.

4. Models were solved using trial and error to determine which voltageyielded the electric field contour of 650 V/cm in the shape of alemniscate of Bernoulli.

5. The determined voltage was placed into the Cassini oval electronicworksheet for the same electrode geometry and the “gain denominator” wasadjusted until the shape from the cassini oval matched that from thenumerical solution.

6. The determined gain denominators for all values of “a” were collectedand a calibration plot was made and fitted with a logarithmic trendlineof:Gain Denominator=595.28·ln(a)+2339;R ²=0.993  (7)

7. The calibration trendline function shown above was incorporated backinto the Cassini Oval spreadsheet. At this point, the worksheet wascapable of outputting a field contour of 650 V/cm for any electrodeseparation distance (±a) and applied voltage (V).

8. The calibration function was then scaled to a desired electric fieldcontour input. This allowed the analytical solution to solve for anyelectric field for any given a separation distance and voltage. Sincethe Laplace equation is linear, scaling should provide a good estimatefor how other fields would look.

Table 1 incorporates all the steps above to yield a single, calibratedCassini Oval output that analytically predicts the electric fielddistribution; providing a quick and simple solution for the predictionof IRE (irreversible electroporation) treatment regions that may beadjusted in real-time. The inputs are the electrode location (as a given“±a” distance from the origin along the x-axis), the applied voltage tothe energized electrode, and the desired electric field to visualize.The resulting output is a contour representing a threshold where theentire area within it has been subjected to an electric field the oneselected; and thus treated by IRE. It is important to remember that theanalytical solution was calibrated for an electric field contour of 650V/cm, and thus yields an accurate approximation for this value. Otherfield strength contours of interest still yield reasonable results thatmimic the overall shape of the electric field. Overall, the analyticalsolution provided yields consistently good predictions for electricfield strengths, and thus, treatment regions of IRE that may be usedduring treatment planning or analysis.

A similar algorithm for calibration can be used for a bipolar electrode.

In one example, the diameter of the probe is 0.065 cm, and the lengthsof the two electrodes are respectively 0.295 cm and 0.276 cm, separatedby an insulation sleeve of 0.315 cm in length. Adapting this scenario tothe cassini oval presents some challenges because the distribution isnow resulting from the two exposed cylinder lengths, rather than twodistinct loci of points. This was solved by calibrating individualelectric field contours for the same applied voltage and developing twoequations that adjust the separation distance (±a) and gain denominator(GD) according to the equations:a=7*10⁻⁹ *E ³−2*10⁻⁵ *E ²+0.015*E+6.1619;R ²=0.9806  (8)GD=1.0121*E+1920;R ²=0.9928  (9)

-   -   where E is the electric field magnitude contour desired.        These two equations may then be used to calibrate the cassini        ovals into a satisfactory shape to mimic the electric field        distribution, and thus treatment region accordingly.

FIG. 6 illustrates an example of how to generate a combined treatmentzone according to the invention. Three electrodes 201, 202, 203 definingthree individual treatment zones 311, 312, 313, combine to form acombined treatment region 315 which is shown with hatched lines. Bycombining a plurality of treatment zones with each treatment zone beingdefined by a pair of electrodes, a combined treatment region 315 can bedisplayed on the x-y grid.

FIG. 7 illustrates one embodiment of a pulse generator according to thepresent invention. A USB connection 52 carries instructions from theuser computer 40 to a controller 71. The controller can be a computersimilar to the computer 40 as shown in FIG. 2. The controller 71 caninclude a processor, ASIC (application-specific integrated circuit),microcontroller or wired logic. The controller 71 then sends theinstructions to a pulse generation circuit 72. The pulse generationcircuit 72 generates the pulses and sends electrical energy to theprobes. In the embodiment shown, the pulses are applied one pair ofelectrodes at a time, and then switched to another pair using a switch74, which is under the control of the controller 71. The switch 74 ispreferably an electronic switch that switches the probe pairs based onthe instructions received from the computer 40. A sensor 73 such as asensor can sense the current or voltage between each pair of the probesin real time and communicate such information to the controller 71,which in turn, communicates the information to the computer 40. If thesensor 73 detects an abnormal condition during treatment such as a highcurrent or low current condition, then it will communicate with thecontroller 71 and the computer 40 which may cause the controller to senda signal to the pulse generation circuit 72 to discontinue the pulsesfor that particular pair of probes.

The treatment control module 54 can further include a feature thattracks the treatment progress and provides the user with an option toautomatically retreat for low or missing pulses, or over-current pulses(see discussion below). Also, if the generator stops prematurely for anyreason, the treatment control module 54 can restart at the same pointwhere it terminated, and administer the missing treatment pulses as partof the same treatment.

In other embodiments, the treatment control module 54 is able to detectcertain errors during treatment, which include, but are not limited to,“charge failure”, “hardware failure”, “high current failure”, and “lowcurrent failure”.

According to the present invention, irreversible electroporation (IRE)ablation (n=81, where n is the number of IRE ablation procedures) wasperformed in-vivo in 22 pig livers using 2-4 IRE electrodes (18 gauge, 2cm long tip) and a NanoKnife™ generator (AngioDynamics, Fremont, Calif.)as described in the IRE Treatment Application referenced above and asshown in FIGS. 1, 2 and 7. Cardiac-gated (i.e., synchronized to cardiaccycle) 100 μsec IRE pulses were applied sequentially between electrodepairs at 3,000-3,400V (one pair at a time).

Multiple variables for energy deposition and electrode configurationwere studied including: inter-electrode spacing (1.5 cm-3 cm); thenumber of IRE pulses applied between electrode pairs (c=10, 50, & 100);and the order and number of times/cycles each electrode pair wasactivated.

For c=10, a sequence of delivered pulses are as follows: 10 sequentialIRE pulses were delivered per electrode pair for all pairs (e.g., 10pulses for pair 1-2, then 10 pulses for pair 2-3 and then 10 pulses forpair 3-1 for a 3-electrode array). Then the same sequence is repeated 2to 44 times for a total number of IRE pulses delivered of 20 to 440 perelectrode pair. Electrode phase (polarity) was changed after eachsequence (1-2, 2-3, 3-1; 2-1, 3-2, 1-3), which reduces gas buildup nearthe electrodes to thereby reduce the chance of sparks. In oneexperiment, a total of 90 IRE pulses were delivered for each electrodepair.

For c=50, a sequence of 50 IRE pulses were delivered per electrode pairfor all pairs. Then the same sequence is repeated one more time for atotal number of IRE pulses delivered of 100 per electrode pair.

For c=100, a sequence of 100 sequential IRE pulses were delivered pereach electrode pair. Then the same sequence is repeated one more timefor a total number of IRE pulses delivered of 200 per electrode pair.

Between two pulses, two electrode pairs and two sequences, there is awaiting (delay) period. The reasons for the waiting period are todissipate any thermal buildup in the tissue cells, especially around theelectrodes where the current density is highest, and to increase theablation zone.

Preferably, the generator 10 inserts a time delay between two pulses(inter-pulse delay) of at least 250 ms (milliseconds) and at most 15seconds, and more preferably at least 1 second and at most 8 seconds. Atgreater than 8 seconds, the ablation zone does not increase and actuallymay help to decrease it.

Preferably, the generator 10 inserts a time delay of 5 seconds to 10minutes between electrode pairs (inter-pair delay) within a sequence.Preferably, the generator inserts a time delay of 5 seconds to 20minutes between two sequences (inter-sequence delay).

With a single IRE pulse, the cells try to close the holes/pores createdin the membrane within a fraction of a second. By applying multiplepulses with inter-pulse, inter-pair and inter-sequence delays, it isbelieved that the cells' attempt to repeatedly close the holes exhausttheir ability to close them, which thereby increases the ablation zone.

Ablations were performed under ultrasound guidance. Dimensions ofresultant zones of treatment were measured by ultrasound 1-3 hrpost-procedure and confirmed at gross and histopathology. These data andablation times were compared and subject to statistical analysis todetermine optimal pulse parameters.

Although the experiments involved 10, 50 and 100 pulses in a sequence,the general inventive concept can be expanded to include as little as 1pulse per electrode pair in a sequence. In other words, for a 3electrode array, a sequence of 1 IRE pulse per electrode pair is appliedfor all three pairs. Then, the sequence is repeated for 70 to 100 times.Preferably, the number of pulses for each electrode pair in a singlesequence can vary between 1 and 280.

Currently, the NanoKnife generator is programmed to deliver a single IREpulse per cardiac cycle if a cardiac-sync is selected. In a 3 or moremulti-electrode array, more than one IRE pulse per cycle can bedelivered by switching electrodes using the switch 74. For example, in a3 electrode-array arrangement, in a single cardiac cycle, a sequence ofsingle IRE pulse between pair 1-2, between pair 2-3 and between pair 2-3can be applied for a total of 3 IRE pulses delivered, for example,within an R-wave of the cycle.

Alternatively, for applying 100 pulses, a sequence of 10 IRE pulsesbetween pair 1-2, then between pair 2-3 and then between pair 2-3 can beapplied for a total of 10 sets to deliver a total of 100 pulses for eachelectrode pair. For applying 500 pulses, a sequence of 10 IRE pulses canbe sequentially applied to the 3 electrode pairs for a total of 50 sets.For applying 1000 pulses, a sequence of 10 IRE pulses can besequentially applied to the 3 electrode pairs for a total of 100 sets.

The IRE pulses can be unipolar pulses or alternating polarity pulsessuch as biphasic pulses or consecutive positive and negative pulsesseparated by a slight time delay.

According to the experiments, the largest contiguous zones of treatmenteffect (6.4±0.6 cm width and length, 3.7±1.4 cm height) were achievedapplying 2 cycles (sequences) of 50 IRE pulses sequentially to allelectrode pairs within a 4 electrode array of 2.5 cm spacing (totaltime=17.5±6.7 min). For 4 electrode arrays, treatment diameter bestcorrelated with overall time of the energy application [r2=0.71]).Greatest ablation for 3 electrode arrays (5.9±0.4 cm×5.3±0.5 cmcross-sectional area) was achieved by continuously delivering 10 pulsessequentially to each of the 3 electrode pairs for 10-12 min. For 2electrode arrays using similar energy application strategies, ablationof only 3.9±0.5 cm length with variable width (incomplete to 2.4 cm) wasachieved.

In another experiment, IRE ablation procedures were performed on porcineliver using the following parameters: 2.5 cm spacing between theelectrodes, 100 μs pulses, 3 kVolts, 2 cm exposed electrodes, and100-1000 pulses delivered. FIG. 8 is a graph illustrating therelationship of the number of pulses delivered to a pair of electrodesand the size of the actual ablation region in this experiment.

As can be seen, there is generally a positive correlation between thenumber of pulses (and therefore the total pulse application time) andthe size of the ablation region although the rate of increase slows asmore pulses are applied. For length, it varied between 4 cm and 5.7. Forwidth, it varied between 1.5 cm and 3.3 cm. Using a curve fittingalgorithm, the graph for length and width produced the followingformulas:

y=1.6832*x{circumflex over ( )}0.1849, where x=length in centimeter, and

y=0.3407*x{circumflex over ( )}0.3381, where x=width in centimeter.

Table 2 below summarizes the experimental data in terms of the increasein size in two dimensions (area) and three dimensions (volume).

TABLE 2 Length of 2-D 3-D Width of ablated ablated % ablated % # of 100ablated region region increase volume increase μs pulses region(cm) (cm)(cm{circumflex over ( )}2) in area (cm{circumflex over ( )}3) in volume100 1.5 4 6 NA 24 NA 600 2.9 5.5 15.95 166% 87.725 266% 1000 3.3 6 19.8230% 118.8 395%

As seen above, for two dimensional regions, increasing the number ofpulses from 100 to 600 and 1000 respectively produced a surprisinglylarge increase of 166% and 230% in ablation area. If an assumption ismade that the increase in depth is similar to the increase in length,then increasing the number of pulses from 100 to 600 and 1000respectively produces an increase of 266% and 395% in ablation volume.

Based on the above relationship between the ablation size and the numberof delivered pulses, calculation of the estimated treatment region canbe adjusted accordingly. For example, if the experimental data show thatthe shape of the treatment region increases proportionally (width,length and depth of the region), then the term b{circumflex over ( )}2in the Cassini oval equation may be adjusted accordingly. If, however,the shape of the treatment region increases in a non-proportional manner(e.g., length increases at twice the rate as the width), then theCassini oval equation can be modified by adding or subtracting aconstant to the b{circumflex over ( )}2 term (e.g., b{circumflex over( )}2+/−C) as well as adjusting the b{circumflex over ( )}2 term itself.Alternatively, the number of electrodes can be reduced.

Aside from varying the number of applied pulses, varying the width ofeach pulse from 20 microseconds to 100 microseconds produced a slightincrease in the ablation size. Increasing the pulse width, however, alsoreduced the variance in ablation size (i.e., reduction in standarddeviation). As the pulse width increased past 50-70 microseconds, thevariance among the ablation sizes decreased substantially. This effectbecame more pronounced for longer spacing between the electrodes (e.g.,greater than 3 cm). Thus, this information could also be used toincrease the ablation size and also to more accurately predict theablation size.

In procedures involving 3 or more electrodes, rather than applying thetotal number of electrodes sequentially for each pair, then moving on tothe next pair, dividing up the total number of pulses to be deliveredinto smaller subsets and then applying each subset of pulses to eachpair, and then repeating the sequence for the subsequent subsets whilereversing the polarity for each sequence (i.e., E1(+)−E2(−), thenE2(+)−E1(−) in the next sequence) produced an increase in the ablationsize, especially when the total number of pulses for each pair wassubstantially higher than 100.

For a 3-electrode procedure and the total number of pulses=500, forexample, the sequence of delivered pulses are as follows: 10 sequentialIRE pulses per electrode pair for all pairs (e.g., 10 pulses for pair1-2, then 10 pulses for pair 2-3 and then 10 pulses for pair 3-1). Thenthe same sequence is repeated 50 times for a total number of IRE pulsesdelivered of 500 per electrode pair with the electrode phase (polarity)being reversed after each sequence.

FIG. 9 illustrates ablation regions of different sizes that aredisplayed on the monitor 11 according to the number of pulses delivered.The original lesion or target area 300 has been increased to an enlargedtarget region 301 which adds a margin of error. The estimated ablationarea 305 has been generated assuming that 100 pulses will be deliveredwith four electrodes positioned as shown (superimposed over the targetregion 301). As can be seen, the estimated ablation/treatment area 305barely covers the original target area 300 and is clearly inadequate tocover the enlarged target region 301.

However, according to the present invention, the enlarged target region301 can be adequately covered by an increased ablation area 325 whichhas been calculated based on 1000 pulses (and which has beensuperimposed over the target region 301). Since such a large treatmentarea 325 can damage too much of good tissue, after receivingidentification of a target region, the treatment control module 54 canselect/adjust the number of pulses or number of electrodes, or both sothat the resulting estimated treatment area sufficiently covers thetarget region 301 while minimizing ablation of good tissue. One way todo so is to generate a plurality of estimated ablation regions based ona plurality of pulse count, and then selecting the minimum pulse countthat completely covers the target region 301 while minimizing damage togood tissue.

Advantageously, the present invention allows treatment of largerablation regions with fewer electrodes to thereby provide a safer andless expensive electrical ablation procedure for patients. The presentinvention also allows treatment of a larger ablation area withoutdividing up the area into multiple regions and repeating the procedure.

The above disclosure is intended to be illustrative and not exhaustive.This description will suggest many modifications, variations, andalternatives may be made by ordinary skill in this art without departingfrom the scope of the invention. Those familiar with the art mayrecognize other equivalents to the specific embodiments describedherein. Accordingly, the scope of the invention is not limited to theforegoing specification.

What is claimed is:
 1. A device for delivery of electrical energy to atarget tissue during a treatment procedure, the device comprising: agenerator, a processor, a memory, a display unit coupled to theprocessor, and a treatment control module, the processor coupled to thegenerator, the memory, and the treatment control module; the generatorto deliver a number of electrical pulses to the target tissue during thetreatment procedure, when executed by the processor, the treatmentcontrol module: receives identification of a target region; generates anenlarged target region comprising a margin surrounding the identifiedtarget region; generates an estimated treatment region; and generates aresulting estimated treatment area by adjusting an at least onetreatment parameter such that the resulting estimated treatment areasufficiently covers the enlarged target region while minimizing ablationof good tissue; and wherein the display unit to display the resultingestimated treatment area superimposed over the estimated treatmentregion.
 2. The device of claim 1, wherein the treatment procedure isirreversible electroporation.
 3. The device of claim 1, wherein thegenerator to operatively couples to at least two probes.
 4. The deviceof claim 3, wherein the at least one treatment parameter is a number ofthe at least two probes to be used during the treatment procedure. 5.The device of claim 3, wherein the treatment control module furtherselects the number of the at least two probes to be used during thetreatment procedure.
 6. The device of claim 5, wherein the estimatedtreatment region is enlarged to the enlarged target region by changingthe number of the at least two probes to be used during the treatmentprocedure.
 7. The device of claim 1, wherein the at least one treatmentparameter is the number of electrical pulses generated by the generatorto be delivered during the treatment procedure.
 8. The device of claim1, wherein the estimated treatment region is enlarged to the enlargedtarget region by changing the number of electrical pulses to be usedduring the treatment procedure.
 9. The device of claim 8, wherein thegenerator generates the changed number of electrical pulses to be usedduring the treatment procedure.
 10. The device of claim 1, wherein auser selects a treatment parameter.
 11. The device of claim 1, wherein auser adjusts the margin.
 12. A device for delivery of electrical energyto a target tissue site during an ablation procedure, the devicecomprising: a treatment console comprising a generator, a processor, amemory, and a treatment control module, the processor coupled to thememory, and the treatment control module; the generator to deliver anumber of electrical pulses to the target tissue site during theablation procedure, the generator coupled to the processor; and thetreatment control module to be stored in the memory, and when executedby the processor, the treatment control module to: receiveidentification of a target region; generate an enlarged target regioncomprising a margin surrounding the identified target region; generatean estimated treatment region; generate a resulting estimated treatmentarea by adjusting at least one treatment parameter so that the resultingestimated treatment area sufficiently covers the enlarged target regionwhile minimizing ablation of good tissue; generate a plurality ofresulting estimated treatment regions by adjusting an at least onetreatment parameter; and select, from the plurality of resultingestimated treatment regions, the resulting estimated treatment area withthe smallest size that covers the enlarged target region.
 13. The deviceof claim 12, wherein the generator to operatively couple to at least twoelectrodes.
 14. The device of claim 13, wherein the at least onetreatment parameter is the number of the at least two electrodes. 15.The device of claim 12, wherein the treatment control module is furtherconfigured to determine if the resulting estimated treatment region doesnot sufficiently cover the enlarged target region.
 16. The device ofclaim 15, further comprising a display unit coupled to the processor,the display unit to display the at least one treatment parameter. 17.The device of claim 16, wherein the display unit to display the targetregion superimposed with the estimated treatment region.
 18. The deviceof claim 12, wherein the at least one treatment parameter is the numberof electrical pulses to be delivered to the target region.
 19. A devicefor delivery of pulsed electrical energy to a target tissue during atreatment procedure, the device comprising: a processor, a memory, and atreatment control module, the processor coupled to the memory and thetreatment control module; the treatment control module to be stored inthe memory and when executed by the processor the treatment controlmodule to: receive identification of a target region; and generate anenlarged target region comprising a margin surrounding the identifiedtarget region; generates an estimated treatment region; generate aresulting estimated treatment area by adjusting at least one treatmentparameter so that the resulting estimated treatment area sufficientlycovers the enlarged target region while minimizing ablation of goodtissue; determine if the estimated treatment region does notsufficiently cover the enlarged target region; generate a plurality ofestimated treatment regions based on a plurality of electrical energypulse counts; and select a minimum number of electrical energy pulses tobe delivered that covers the enlarged target region.